Drug dependence and addiction caused by drug-taking and drug abuse have become an increasingly serious social problem. Common therapies include substitution and gradual withdrawal therapy (such as Methadone and Dihydroetorphine etc), subhibernation therapy, Chinese medicine therapy and the like. However, there is no accepted and ideal method available up to date.
Currently the mechanism underlying addiction to opioids is believed to be related to the function of opioid receptors. Under normal physiological conditions, opioid receptors are subjected to the action of certain basal level of endogenous opioid peptides (EOP). When exogenous opioid compounds (EOC) such as morphine are given, morphine will occupy the rest of opioid receptors, thereby enhancing the analgesic effects of endogenous opioid peptides. When exogenous morphine is given successively and in excess, the release of EOP from EOP neurons will decrease sharply through feedback regulation, and more exogenous morphine will be needed to maintain the analgesic effects. Therefore, once drugs such as morphine are stopped, neither endogenous opioid peptides nor exogenous morphine is available to act on opioid receptors, and a series of abnormal symptoms due to increased secretion of other neurotransmitters will appear, clinically known as withdrawl syndrome.
Normal organisms have cells that can secret endogenous opioid peptides, such as medulliadrenal chromaffin cells (MCCs) and the like. MCC can secret three types of substances: monoamines, such as norepinephrine (NE), epinephrine (E), dopamine and the like; endogenous opioid peptides, such as leucine-enkephalin, methionine-enkephalin, dynorphin and the like; and various growth factors, such as nerve growth factor, epidermal growth factor and the like. MCC, upon relevant stimulations, can secret corresponding substances, producing stress and analgesic effects. In the beginning of 1980's, two research groups from USA and Switzerland tried to implant homogenous (human, rat) adrenal medulla tissues and chromaffin cells into subarchnoid space of spinal cord for treating pain and had finally obtained satisfactory results. Because of the rare sources of human adrenal medulla tissues and chromaffin cells, in 1990's, the research group from USA had tried to implant heterogeneous bovine adrenal medulla chromaffin cells (hereafter abbreviated as BCCs) into subarachnoid space of cancer patients to cure pain. In order to overcome the immune rejection, they used polyacrylamide hollow fiber tube of 5 cm in length and 1 mm in diameter to coat BCCs. As said hollow fiber tube only allow small molecules to pass through, the secretion of BCCs can diffuse slowly and uniformly out of the fiber tube to exert the analgesic effect, while macromolecular immunoglobulin in host body cannot pass through the hole of tube wall, so that the cells can survive in host body for a long period (about 1 year) and allows continuous delivery of analgesic substances to treat the patients suffering from pain. But the hollow fiber tube has a large volume. On one side, the dead volume of tube affect the dispersion of nutrients and metabolites, which make the cells inside tube can't survive chronically. On the other hand, implantation of fiber tube with large volume into subarachnoid space would stimulate and oppress spinoneure, thereby cause many undesirable side effects. Moreover, as the volume of hollow fiber tube is large, it must to be implanted into subarachnoid space by surgical operation, which would injure patient more or less. In the meantime, the hollow fiber tube made of materials such as chitosan, polyacrylamide and sodium carboxymethylcellulose (used in USA) has poor tissue biocompatibility, which causes tissue reaction in host body. On the other side, the microcapsules with three layer membrane structure of sodium alginate-polylysine-sodium alginate (hereafter APA microcapsule) have little volume (200-1000 μm in diameter) and high biocompatibility, which facilitates the long intact presence of the microcapsule in host cell and the long survival of the cells inside microcapsule. The experiments have indicated that microcapsule membrane can cut off macromolecule with molecular weight beyond 110,000 Kd (dalton), prevent immunoglobulin and immunological competent cells pass through said membrane into microcapsule to destroy the animal cells inside, which thus provide proper immune protection. Experiments also indicated that APA microcapsules have proper biocompatibility, and have long term existence (about one year and half) in small or big animal body. The research on implantation of islands of Langerhans, liver cells, parathyroid and genetic recombinant growth-hormone secretory cells for treating disease model animal have provided the evidence that said APA microcapsule protect heterogeneous implant from host immune system. However, so far, there is no report worldwide about use of APA microencapsulated bovine medulliadrenal chromaffin cells for treating and/or relieving withdrawl syndrome.